This competing renewal proposal requests support for the General Clinical Research Center (GCRC) at the LAC+USC Medical Center (University of Southern California) which has been continuously funded by the National Institutes of Health for the past 33 years. This 3-bed outpatient and 13-bed inpatient unit serves as the major primary resource for the performance of high quality investigation in a controlled environment at a very large and active medical center. Since its opening in 1959, the program has been highly successful in expanding its physical resources along with a parallel increase in research productivity (1121 total publications including 103 this past year). In the last two years, the GCRC has experienced a marked increase in research activity as reflected both by an increased inpatient census (>125 % of funded beds) as well as a 40 to 100% greater demand for support services. As an interim step to meet this demand, an enlarged outpatient unit was constructed; nursing, dietary and core laboratory programs were expanded and a successful supplement grant funded construction of a relocated remodeled GCRC facility (14 inpatient beds and 5 outpatient). Specialized core laboratories have also been developed including a Molecular Core, Divalent Cation and a Low Level Ligand Detection facilities, thereby allowing new technologies to be applied to a variety of GCRC projects. Major new NIH-sponsored projects concerning diabetes-atherosclerosis, SCOR-hypertension and sickle cell anemia have been implemented during this grant period along with expansion of research programs relating to adults, mothers and neonates afflicted with HIV infections and related diseases. In the next grant period, it is proposed to: 1) enlarge the specialized laboratory activities, 2) initiate a training program for clinical investigators, 3) foster growth of HIV-related research programs, 4) continue to diversify research activities including development of programs relating to reemergent non-HIV infectious diseases, biology of surgical injury response, pulmonary dysfunction associated with prematurity and gene therapy.